Abstract
Molecular mimicry is defined as similar structures shared by molecules from dissimilar genes or by their protein products. Either several linear amino acids or their conformational fit may be shared, even though their origins are separate. Hence, during a viral or microbe infection, if that organism shares cross-reactive epitopes for B or T cells with the host, then the response to the infecting agent will also attack the host, causing autoimmune disease. A variation on this theme is when a second, third, or repeated infection(s) shares cross-reactive B or T cell epitopes with the first (initiating) virus but not necessarily the host. In this instance, the secondary infectious agents increase the number of antiviral/antihost effector antibodies or T cells that potentiate or precipitate the autoimmune assault. The formation of this concept initially via study of monoclonal antibody or clone T cell cross-recognition in vitro through its evolution to in vivo animal models and to selected human diseases is explored in this mini-review.
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Atkinson MA, Bowman MA, Campbell L, Darrow BL, Kaufman DL, MacLaren NK (1994) Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J Clin Invest 94:2125–2129
Bachmaier K, Neu N, de la Maza LM, Pal S, Hessel A, Penninger JM (1999) Chlamydia infections and heart disease linked through antigenic mimicry. Science 283:1335–1339
Brewerton D, Caffrey M, Hart F, James D, Nichols A, Sturrock R (1973) Ankylosing spondylitis and HLA B27. Lancet i:904–907
Cunningham MW (2004) T cell mimicry in inflammatory heart disease. Mol Immunol 40:1121–1127
Cunningham MW, Fujinami RS (eds) (2000) Molecular mimicry. ASM Press, Washington DC
Dales S, Fujinami RS, Oldstone MBA (1983a) Serologic relatedness between Thy1.2 and actin revealed by monoclonal antibody. J Immunol 131:1332–1338
Dales S, Fujinami RS, Oldstone MBA (1983b) Infection with vaccinia favors the selection of hybridomas synthesizing auto-antibodies against intermediate filaments, among them one cross-reacting with the virus hemagglutinin. J Immunol 131:1546–1553
Dell A, Antone SM, Gauntt CJ, Crossley CA, Clark WA, Cunningham MW (1991) Autoimmune determinants of rheumatic carditis: localization of epitopes in human cardiac myosin. Eur Heart J 12:158–162
Dixon FJ (1963) The role of antigen antibody complexes in disease. Harvey Lecture 58:21–52
Dyrberg T, Oldstone MBA (1986) Peptides as probes to study molecular mimicry and virus-induced autoimmunity. Curr Topics Microbiol Immunol 130:25–37
Dyrberg T, Petersen JS, Oldstone MBA (1990) Immunological cross-reactivity between mimicking epitopes on a virus protein and a human autoantigen depends on a single amino acid residue. Clin Immunol Immunopathol 54:290–297
Eastmond CJ, Woodrow JC (1977) Discordance for ankylosing spondylitis in monozygotic twins. Ann Rheum Dis 36:360
Ebers G, Bulman D, Sadovnik A, Paty DW, Warren S, Hader W, Murray TJ, Seland TP, Duquette P, Grey T et al. (1987) A population-based study of multiple sclerosis in twins. N Engl J Med 315:1638–1642
Froude J, Gibofsky A, Buskirk DR, Khana A, Zabriskie JB (1989) Reactivity between streptococcus and human tissue. Curr Topics Microbiol Immunol 145:5–26
Fujinami RS, Oldstone MBA (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: Mechanism for autoimmunity. Science 230:1043–1045
Fujinami RS, Oldstone MBA, Wroblewska Z, Frankel ME, Koprowski H (1983) Molecular mimicry in virus infection: cross-reaction of measles phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci USA 80:2346–2350
Gamble DR (1980) The epidemiology of insulin-dependent diabetes with particular reference to the relationship of virus infection to its etiology. Epidemiol Rev 2:49–70
Gilliland B, Mannik M (1986) Ankylosing spondylitis and Reiter’s syndrome (pp 1986–1988) and rheumatoid arthritis (pp 1977–1986). In: Harrison TR (ed) Harrison’s Principles of Internal Medicine, 10th Edition. McGraw Hill, New York
Green A (1990) The role of genetic factors in development of IDDM. Curr Topics Microbiol Immunol 164:3–17
Hafer-Macko C, Hsieh ST, Li CY, Ho TW, Sheikh K, Cornblath DR, McKhann GM, Asbury AK, Griffin JW (1996) Acute motor axonal neuropathy: an antibody-mediated attack on axolemma. Ann Neurol 40:635–644
Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD (1990) Spontaneous inflammatory disease in transgenic mice expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders. Cell 63:1099–1112
Honeyman MC, Stone NL, Harrison LC (1998) T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. Mol Med 4:231–239
Hudrisier D, Riond J, Burlet-Schiltz O, von Herrath MB, Lewicki H, Monsarrat B, Oldstone MBA, Gairin JE (2001) Structural and functional identification of major histocompatibility complex class I-restricted self-peptides as naturally occurring molecular mimics of viral antigens. J Biol Chem 276:19396–19403
Jury KM, Loeffler D, Eiermann TH, Ziegler B, Boehm BO, Richter W (1996) Evidence for somatic mutation and affinity maturation of diabetes associated human autoantibodies to glutamate decarboxylase. J Autoimmun 9:371–377
Kaplan MH (1963) Immunologic reactivity of streptococcal and tissue antigens. J Immunol 90:595–606
Khare SD, Luthra HS, David CS (1996) Role of HLA-B27 in spondyloarthropathies. Curr Topics Microbiol Immunol 206:85–97
Kurtzke JF (1993) Epidemiologic evidence for multiple sclerosis as an infection. Clin Microbiol Rev 6:382–427
LaFace DM, Vestberg M, Yang Y, Srivastava R, Di Santo J, Flomenberg N, Brown S, Sherman LA, Peterson PA (1995) Human CD8 transgene regulation of HLA recognition by murine T cells. J Exp Med 182:1315–1325
Lane DP, Hoeffler WK (1980) SV40 large T shares an antigenic determinant with a cellular protein of molecular weight 68,000. Nature 288:167–170
Mason D (1998) A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol Today 19:395–404
Merriman TR, Todd JA (1995) Genetics of autoimmune disease. Curr Opin Immunol 7:786–792
Notkins AL, Yoon JW (1984) Virus-induced diabetes mellitus. In: Notkins AL, Oldstone MBA (eds) Concepts in Viral Pathogenesis. Springer-Verlag, New York, pp 241–247
Oldstone MBA (1987) Molecular mimicry and autoimmune disease. Cell 50:819–820
Oldstone MBA (ed) (1989) Molecular mimicry. Curr Topics Microbiol Immunol, Vol. 145
Oldstone MBA (1998) Molecular mimicry and immune-mediated diseases. FASEB J 12:1255–1265
Oldstone MBA, von Herrath M, Lewicki H, Hudrisier D, Whitton JL, Gairin JE (1999) Use of a high-affinity peptide that aborts MHC-restricted cytotoxic T lymphocyte activity against multiple viruses in vitro and virus-induced immunopathologic disease in vivo. Virology 256:246–257
Panitch HS (1994) Influence of infection on exacerbations of multiple sclerosis. Ann Neurol 36:S25
Rath HC, Herfarth HH, Ikeda JS, Grenther WB, Hamm TE Jr, Balish E, Taurog JD, Hammer RE, Wilson KH, Sartor RB (1996) Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rates. J Clin Invest 98:945–953
Schwimmbeck P, Oldstone MBA (1989)Klebsiella pneumoniae and HLA B27 associated diseases of Reiter’s syndrome and ankylosing spondylitis. Curr Topics Microbiol Immunol 145:45–67
Schwimmbeck PL, Dyrberg T, Drachman D, Oldstone MBA (1989) Molecular mimicry and myasthenia gravis: An autoantigenic site of the acetylcholine receptor α-subunit that has biologic activity and reacts immunochemically with herpes simplex virus. J Clin Invest 84:1174–1180
Schwimmbeck PL, Yu DTY, Oldstone MBA (1987) Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter’s syndrome: Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease. J Exp Med 166:173–181
Shrinivasappa J, Saegusa J, Prabhakar B, Gentry M, Buchmeier M, Wiktor T, Koprowski H, Oldstone M, Notkins A (1986) Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J Virol 57:397–401
Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, Balish E, Hammer RE (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic mice. J Exp Med 180:2359–2364
Theofilopoulos A (1995) The basis of autoimmunity. II. Genetic predisposition. Immunol Today 16:150–159
Tishon A, LaFace DM, Lewicki H, van Binnendijk RS, Osterhaus A, Oldstone MBA (2000) Transgenic mice expressing human HLA and CD8 molecules generate HLA-restricted measles virus cytotoxic T lymphocytes of the same specificity as humans with natural measles virus infection. Virology 275:286–293
Tonietti G, Oldstone MBA, Dixon FJ (1970) The effect of induced chronic viral infections on the immunologic diseases of New Zealand mice. J Exp Med 132:89–109
Wucherpfennig KW, Strominger JL (1995) Molecular mimicry in T-cell mediated autoimmunity: viral peptides activate human T-cell clones specific for myelin basic protein. Cell 80:695–705
Yoon JW, Austin M, Onodera T, Notkins AL (1989) Virus-induced diabetes mellitus: isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300:1173–1179
Yuki N, Susuki K, Koga M, Nishimoto Y, Odaka M, Hirata K, Taguchi K, Miyatake T, Furukawa K, Kobata T, Yamada M (2004) Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome. Proc Natl Acad Sci USA 101:11404–11409
Zhao ZS, Granucci F, Yeh L, Schaffer P, Cantor H (1997) Molecular mimicry by herpes simplex virus type 1: autoimmune disease after viral infection. Science 79:1344–1347
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Oldstone, M.B.A. (2005). Molecular Mimicry, Microbial Infection, and Autoimmune Disease: Evolution of the Concept. In: Oldstone, M.B. (eds) Molecular Mimicry: Infection-Inducing Autoimmune Disease. Current Topics in Microbiology and Immunology, vol 296. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-30791-5_1
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DOI: https://doi.org/10.1007/3-540-30791-5_1
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-25597-0
Online ISBN: 978-3-540-30791-4
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Keywords
- Ankylose Spondylitis
- Experimental Autoimmune Encephalomyelitis
- Myelin Basic Protein
- Molecular Mimicry
- Encephalitogenic Site
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